3-120059642-T-C

Variant names:

• chr3-120059642-T-C
• rs2199503
• NM_001146156.2:c.88+33705A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146156.2(GSK3B):​c.88+33705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,160 control chromosomes in the GnomAD database, including 47,993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47993 hom., cov: 32)
• Consequence: GSK3B NM_001146156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 24 publications found

Genes affected

GSK3B (HGNC:4617): (glycogen synthase kinase 3 beta) The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]

GSK3B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics

ENSG00000288662 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.88+33705A>G		intron_variant	Intron 1 of 10	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.88+33705A>G		intron_variant	Intron 1 of 11		NP_002084.2
GSK3B	NM_001354596.2	c.88+33705A>G		intron_variant	Intron 1 of 9		NP_001341525.1
GSK3B	XM_006713610.4	c.88+33705A>G		intron_variant	Intron 1 of 10		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.88+33705A>G		intron_variant	Intron 1 of 10	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119594 AN: 152042 Hom.: 47927 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.777

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.787 AC: 119717 AN: 152160 Hom.: 47993 Cov.: 32 AF XY: 0.784 AC XY: 58320 AN XY: 74372

African (AFR) AF: 0.948 AC: 39360 AN: 41540

American (AMR) AF: 0.790 AC: 12061 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2421 AN: 3472

East Asian (EAS) AF: 0.639 AC: 3311 AN: 5182

South Asian (SAS) AF: 0.800 AC: 3862 AN: 4830

European-Finnish (FIN) AF: 0.700 AC: 7394 AN: 10566

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48929 AN: 67988

Other (OTH) AF: 0.774 AC: 1630 AN: 2106

Alfa AF: 0.742 Hom.: 75775

Bravo AF: 0.799

Asia WGS AF: 0.734 AC: 2550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2199503; hg19: chr3-119778489;